Magic™ Anti-CD19 monoclonal antibody, clone ID38

Competitive swimming requires high training load cycles including consecutive sessions with little recovery in between which may contribute to the onset of fatigue and eventually illness. We aimed to investigate immune changes over a 7-month swimming season. Fifty-four national and international level swimmers (25 females, 29 males), ranging from 13 to 20 years of age, were evaluated at rest at: M1 (beginning of the season), M2 (after the 1st macrocycle's main competition), M3 (highest training load phase of the 2nd macrocycle) and M4 (after the 2nd macrocycle's main competition) and grouped according to sex, competitive age-groups, or pubertal Tanner stages. Hemogram and the lymphocytes subsets were assessed by automatic cell counting and by flow cytometry, respectively. Self-reported Upper Respiratory Symptoms (URS) and training load were quantified. Although the values remained within the normal range reference, at M2, CD8(+) decreased (M1 = 703 +/- 245 vs. M2 = 665 +/- 278 cell mu L-1; p = 0.032) and total lymphocytes (TL, M1 = 2831 +/- 734 vs. M2 = 2417 +/- 714 cell mu L-1; p = 0.007), CD3(+) (M1 = 1974 +/- 581 vs. M2 = 1672 +/- 603 cell mu L-1; p = 0.003), and CD4(+) (M1 = 1102 +/- 353 vs. M2 = 929 +/- 329 cell mu L-1; p = 0.002) decreased in youth. At M3, CD8(+) remained below baseline (M3 = 622 +/- 245 cell mu L-1; p = 0.008), eosinophils (M1 = 0.30 +/- 0.04 vs. M3 = 0.25 +/- 0.03 10(9) L-1; p = 0.003) and CD16(+)56(+) (M1 = 403 +/- 184 vs. M3 = 339 +/- 135 cell mu L-1; p = 0.019) decreased, and TL, CD3(+), and CD4(+) recovered in youth. At M4, CD19(+) were elevated (M1 = 403 +/- 170 vs. M4 = 473 +/- 151 cell mu L-1; p = 0.022), CD16(+)56(+) continued to decrease (M4 = 284 +/- 131 cell mu L-1; p < 0.001), eosinophils remained below baseline (M4 = 0.29 +/- 0.05 10(9) L-1; p = 0.002) and CD8(+) recovered; monocytes were also decreased in male seniors (M1 = 0.77 +/- 0.22 vs. M4 = 0.57 +/- 0.16 10(9) L-1; p = 0.031). The heaviest training load and higher frequency of URS episodes happened at M3. The swimming season induced a cumulative effect toward a decrease of the number of innate immune cells, while acquired immunity appeared to be more affected at the most intense period, recovering after tapering. Younger athletes were more susceptible at the beginning of the training season than older ones.

CD19-directed immunotherapies are clinically effective for treating B cell malignancies but also cause a high incidence of neurotoxicity. A subset of patients treated with chimeric antigen receptor (CAR) T cells or bispecific T cell engager (BiTE) antibodies display severe neurotoxicity, including fatal cerebral edema associated with T cell infiltration into the brain. Here, we report that mural cells, which surround the endothelium and are critical for blood-brain-barrier integrity, express CD19. We identify CD19 expression in brain mural cells using single-cell RNA sequencing data and confirm perivascular staining at the protein level. CD19 expression in the brain begins early in development alongside the emergence of mural cell lineages and persists throughout adulthood across brain regions. Mouse mural cells demonstrate lower levels of Cd19 expression, suggesting limitations in preclinical animal models of neurotoxicity. These data suggest an on-target mechanism for neurotoxicity in CD19-directed therapies and highlight the utility of human single-cell atlases for designing immunotherapies.